InterLymph 2015

What is InterLymph?

The International Lymphoma Epidemiology Consortium (InterLymph) is an open scientific forum for epidemiologic research in non-Hodgkin lymphoma (NHL). Established in 2001, the Consortium is an international collaboration of scientists who undertake research projects that pool data across studies to better understand lymphoma risk factors. Although the main emphasis of the collaboration is epidemiology, InterLymph has expanded to include geneticists, pathologists, immunologists, clinicians and other scientists and now includes more than 100 members. InterLymph consists of four working groups (Immunology and Infection, lifestyle and environment, pathology and survival, genetics), and has evolved to include multiple large scale projects that operate across working groups. In 2014, several large pooling projects have been successfully finalized (see below).

What are the goals of InterLymph?

The overarching goal of InterLymph is to identify patterns of commonality and heterogeneity in the etiology of NHL subtypes which may assist in illustrating mechanisms of lymphomagenesis. This knowledge has implications for understanding biology, etiology, prevention and control of these malignancies. The Consortium aims to achieve this by addressing research questions that are difficult to answer in individual studies, by sharing data and biological samples. The Consortium has established a central data coordinating center that is a repository of pooled, harmonised data from all recently completed international case-control studies of NHL. In recent years, the collaboration has also expanded to several international cohort studies.

Latest findings from InterLymph

We continue our research investigating inherited genetic variants associated with risk of lymphoma and lymphoma subtypes. In addition to our prior publications for follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and Hodgkin lymphoma, we published in 2015 our findings for marginal zone lymphoma (MZL). Specifically, we performed a pooled genome-wide association study (GWAS) that included in total 1,295 cases and 7,127 controls of European ancestry (Vijai et al, Nature Commun 2015; 6:5751). Two independent risk SNPs in the human leukocyte antigen (HLA) were identified. Thus in the lymphoma subtypes we have investigated to date, the HLA genetic region has been identified to be associated with risk for all the subtypes. However, the variants identified within the HLA genetic region differ across the subtypes suggesting still different etiologies. Ongoing genetic studies are being conducted in T-cell lymphoma, mantle cell lymphoma, and waldenstrom macroglobulinemia, as well as further studies in HL, CLL, FL, and DLBCL.

We are now moving forward with studies that evaluate the interaction of genetic variants and lifestyle with risk of lymphoma. In 2015, we have published two studies. The first (Kane et al. Cancer Epi Biomarkers Prev 24(7); 1061-70; 2015) investigated the relationship among obesity, genetic variants, and risk of B-cell NHL in 4,979 cases and 7,452 controls. We continued to show that obesity is associated with DLBCL and that this risk increases to almost two-fold for those who are both obese and have genetic variants located in TNF-α gene. However, for FL and CLL, no associations were observed with obesity alone or in combination with genetic variants. The second study (Wang et al. 2015 Am J Epidemiol 181:406-21) evaluates the relationship among autoimmune conditions, genetic variants, and risk of NHL in 8,692 cases and 9,260 controls. We continue to show that individuals with history of autoimmune conditions haven an increase risk of NHL, specifically in DLBCL, MZL, and peripheral T-cell lymphoma.

These increases are for those individuals with genetic variants within the TNF-α gene; the same gene identified with obsesity. Together these two studies provide additional insight into the biological mechanisms involved in lymphomagenesis. Further studies evaluating the interaction among genetic and environmental factors, including sun exposure and occupational exposures, are ongoing.